He was a boy of 10 when his father, Cosimo II, died in 1621; and his grandmother, Christine of Lorraine, and his mother, Maria Magdalena of Austria, were nominated regents. The young Ferdinand was sent to Rome and Vienna to complete his education, and the government of Tuscany remained in the hands of two jealous and quarrelsome people. Thus the administration of justice and finance speedily went to ruin. They conferred exaggerated privileges on the new Tuscan nobility, which became increasingly insolent. They resumed the old Medicean practice of trading on their own account, and, without reaping much benefit thereby, did the utmost damage to private enterprise.

In 1627 Ferdinand II, then aged 17, returned to Italy and assumed the reins of government; but, being of a very gentle disposition, he decided on sharing his power with the regents and his brothers and arranged matters in such a manner that each was almost independent of the other. He gained the love of his subjects by his great goodness; and, when Florence and Tuscany were ravaged by the plague in 1630, he showed admirable courage and carried out many useful measures. But he was totally incapable of energy as a statesman. He contrived with difficulty to remain neutral, despite pressure from Spain, in the War of the Mantuan Succession (1628–31) and in the later Franco-Spanish hostilities of the Thirty Years’ War. On the other hand, his relations with the papacy were unhappy. Pope Urban VIII’s annexation of Urbino to the Papal States (1626) precluded Ferdinand from acquiring anything more than the freehold property of the former dukes of Urbino when he married their heiress, Vittoria della Rovere, in 1634 (this patrimony, however, included important treasures); and though he allied himself with Venice and Modena to support his brother-in-law Odoardo Farnese, duke of Parma, against Urban during the War of Castro (1642–44) and won a victory at Mongiovino, near Perugia, in 1643, he received no advantage under the treaty of peace.

Deeply religious and austere, Ferdinand II was blamed for his acquiescence to the Holy Office’s treatment of his teacher and protégé Galileo (1633); but he continued to take an interest in science, encouraging his brother Leopoldo, the future cardinal, in the foundation of the Accademia del Cimento in Florence (1657) and offering hospitality to scientists of all nations.